ANALYSIS OF HOXA7 HOXB7 MUTANTS SUGGESTS PERIODICITY IN THE GENERATION OF THE DIFFERENT SETS OF VERTEBRAE/

Mice were generated with targeted disruptions in Hoxa7 and Hoxb7, resp ectively. Mice carrying the Hoxa7 mutation are healthy. No abnormaliti es in the formation of the skeleton or other tissues were found in the se mutants. Twelve percent of Hoxb7-/- mutants show first and second r ib defects similar to those observed in mice homozygous for a Hoxb9 mu tation (Chen, F., Capecchi, M.R., 1997. Dev. Biol. 181, 186-196). Hoxb 7-/- mice are also fertile and were used to generate double mutants wi th Hoxa7 to reveal potential interactions between these two paralogous genes. Mice homozygous for both mutations have first and second rib d efects with higher penetrance and increased expressivity, indicating a functional role for Hoxa7 in the patterning of the upper thoracic reg ion. Although Hoxb6 Hoxa7, Hoxb7, and Hoxb9 have distinctive anterior expression limits in axial mesoderm, the disruptions of these genes al l yield first and second rib defects. A hypothesis is suggested to exp lain the observation that axial defects in these and other mouse Hox m utants appear to concentrate along the axial column at zones of transi tion between vertebral types. (C) 1998 Elsevier Science Ireland Ltd. A ll rights reserved.